Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: a randomized, double-blind, split-face trial.

BACKGROUND: Filler injection has become an extremely popular method for facial skin rejuvenation, including the periorbital area. In the recent years, new polynucleotide (PN)-containing filler products have been used for esthetic purposes. AIM: We aimed to investigate the efficacy and safety of PN filler injection in the periorbital area. PATIENTS/METHODS: A total of 27 subjects were enrolled in this randomized, pair-matched, and active-controlled study. Each subject received filler injections thrice with two-week intervals, with a PN filler injection on one side and a non-crosslinked hyaluronic acid (HA) filler injection on the contralateral side of the periorbital area. RESULTS: Improvements in the visual analog scale and global esthetic improvement scale scores were not significantly different between the PN and HA groups. The improvement rates of skin elasticity and hydration decreased over time in both groups, with the PN group showing a higher improvement rate. The improvement rates of roughness and pore volume were higher in the PN group than in the HA group. The improvement rate of dermal density was not significantly different between the groups. No serious adverse events were reported. CONCLUSION: The PN filler injection is effective and safe for periorbital rejuvenation.

Partial unilateral lentiginosis: a clinicopathological analysis of 32 cases on the head and neck area in Korea.

BACKGROUND: Partial unilateral lentiginosis (PUL) is a rare acquired circumscribed hyperpigmentation characterized by multiple simple lentigines involving half of the body. Since the previous studies of PUL were mostly based on case reports and the current literature lacks well-designed retrospective studies that involve a large number of cases, PUL is not a well-defined entity, and differential diagnosis with nevus spilus is still difficult. This study aims to evaluate clinical and histopathological characteristics and treatment outcomes of PUL on head and neck area of Koreans. METHODS: Thirty-two patients with PUL on head and neck area were diagnosed clinicohistopathologically at the Asan Medical Center from 2004 to 2017. Their medical records, photographs, and biopsy specimens were reviewed, and immunohistochemical staining for protein kinase C (PKC)-ßΙΙ was evaluated for melanogenic activity. RESULTS: Four patients (12.5%) of PUL had congenital lesions, and 24 (75.0%) had age of onset younger than 10 years. Confluency of lentiginous lesions (100%) and mild to moderate background interlesional hyperpigmentation (90.6%) were observed. The lentiginous lesions showed increased melanocytes, melanophages, basal melanins, lentiginous hyperplasia, and perivascular inflammatory cells compared with background interlesional hyperpigmentation, and PKC-ßΙΙ was focally positive in 7 of 12 stained PUL lesions. Among the 16 patients who received laser treatments, 10 (62.5%) showed more than 50% of improvement. CONCLUSIONS: The findings of this study will allow for improved diagnosis of PUL and understanding of its features, which may facilitate proper management in the future.

Ursodeoxycholic Acid May Inhibit Environmental Aging-Associated Hyperpigmentation.

Extrinsic aging of the skin caused by ultraviolet (UV) light or particulate matter is often manifested by hyperpigmentation due to increased melanogenesis in senescent skin. Ursodeoxycholic acid (UDCA), which has been commonly used as a health remedy for liver diseases, is known to possess antioxidant properties. This study was done to investigate whether UDCA inhibits cellular aging processes in the cells constituting human skin and it reduces melanin synthesis. ROS, intracellular signals, IL-1α, IL-8, TNF-α, cyclooxygenase (COX)-2, type I collagen, and matrix metalloproteinases (MMPs) levels were measured in human dermal fibroblasts treated with or without UDCA after UV exposure. Melanin levels and mechanistic pathways for melanogenesis were investigated. UDCA decreased ROS, senescence-associated secretory phenotype (SASP), and proinflammatory cytokines induced by UV treatment. UDCA reduced melanogenesis in normal human melanocytes cocultured with skin constituent cells. Our results suggest that UDCA could be a comprehensive agent for the treatment of environmental aging-associated hyperpigmentation disorders.

"A Multi-center, randomized, double blinded, comparative study of two hyaluronic acid fillers for temporary restoration of mid-face volume in Asians".

BACKGROUND: There have been few studies using hyaluronic acid fillers to restore mid-face volume deficit especially in Asians. AIMS: This study compared the efficacy and safety of two highly cohesive hyaluronic acid fillers, Neuramis® Volume Lidocaine and Juvederm® Voluma® with Lidocaine (VYC-20L), for temporary restoration of mid-face volume in Asians. PATIENTS/METHODS: A total of 88 subjects with moderate to severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received Neuramis® Volume Lidocaine on one side and VYC-20L on the other side of the face. Response was defined as a ≥1 point reduction in MFVDS at 24 weeks after the injection by photographic assessment. Secondary end points included photographic and live assessments of MFVDS and its changes at week 4, 12, and 24; global aesthetic improvements, as assessed by the investigators and the subjects at each visit; and the proportion of subjects who received touch-up treatment. RESULTS: The response rates of the sides treated with Neuramis® Volume Lidocaine and VYC-20L were identical (96.39%) at week 24, demonstrating that Neuramis® Volume Lidocaine was noninferior to VYC-20L. Photographic and live assessments of MFVDS and its changes, global aesthetic improvement, and the proportion of subjects who received touch-up treatment did not differ significantly during follow-up. CONCLUSIONS: Neuramis® Volume Lidocaine was not inferior to VYC-20L in temporarily restoring mid-face volume at 24 weeks after treatment. Both of these highly cohesive hyaluronic acid fillers can be used effectively and safely for the correction of mid-face volume loss in Asians.

Characterization and Prognostic Significance of Cutaneous Adverse Events to Anti-Programmed Cell Death-1 Therapy.

BACKGROUND: Anti-programmed cell death-1 (PD-1) immunotherapy using antibodies such as nivolumab or pembrolizumab has shown promise for treating various types of cancer. In this study, we reviewed the frequency and spectrum of cutaneous adverse events (AEs) caused by PD-1 antibodies and their possible correlation with treatment response. METHODS: We reviewed records of all patients from a single institution treated with either nivolumab or pembrolizumab from August 1, 2014 to April 1, 2017. RESULTS: Of 211 patients included in the study, 134 (63.5%) were treated with nivolumab and 77 (36.5%) with pembrolizumab. Thirty-five patients (16.4%) developed cutaneous AEs. Cutaneous AEs were significantly associated with longer treatment cycles (P = 0.001). The prevalence of cutaneous AEs did not differ between nivolumab (17.2%) and pembrolizumab (15.6%). Patient age, gender, baseline Eastern Cooperative Oncology Group scale and underlying malignancy were not associated with development of cutaneous AEs. Median time until onset of cutaneous AEs was 50.0 days (range, 1-378 days). Anti-PD-1 therapy was tolerable in most of patients with grade 1 (65.2%) and grade 2 (23.9%) cutaneous AEs. Pruritus (32.6%) and eczema (21.7%) were the most commonly reported cutaneous AEs. In lung cancer patients, cutaneous AEs were not associated with better treatment outcomes after adjusting for the number of treatment cycles. CONCLUSION: Both pembrolizumab and nivolumab exhibited tolerable cutaneous safety profiles in a variety of cancer patients undergoing anti-PD-1 therapy. Cutaneous AEs of anti-PD-1 therapy were not associated with antibody type, underlying malignancy, patient characteristics, or improved response.

Anti-aging and hydration efficacy of a cross-linked hyaluronic acid microstructure patch.

This study evaluated the safety and efficacy of biodegradable microstructure patches composed of cross-linked hyaluronic acid (CLHA). A primary skin irritation test showed that the CLHA patches were not an irritant, whereas a clinical study showed that application of single CLHA patches significantly improved skin hydration at the periorbital region for 3 days and at the nasolabial fold for 6 days. Patch application also improved superficial wrinkles at the periorbital region for 3 days and at the nasolabial fold for 1 day. The absence of side effects indicated that application of these CLHA microstructure patches is both safe and convenient for moisturization and anti-wrinkle effects.

Loratadine, an H1 Antihistamine, Inhibits Melanogenesis in Human Melanocytes.

It has long been believed that histamine is associated with cutaneous melanogenesis. Specifically, H2-receptor antagonists reportedly inhibit melanogenesis, but H1-receptor antagonists, which are some of the most commonly prescribed medicines in dermatology, have not been studied to determine whether and how they regulate melanogenesis. Therefore, we screened H1-receptor antagonists to determine whether they inhibit melanogenesis and found that loratadine was particularly effective, in this regard without compromising cellular viability. Loratadine downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase in melanocytes. To determine the intracellular signaling pathways, Akt was consistently activated by loratadine. PI3K/Akt pathway inhibitor, LY294002, restored the reduced melanin content that was induced by loratadine. In addition, phospho-GSK-3ß also was found to be increased following loratadine treatment. Loratadine reduced the amount of PKC-ßII in the membrane fraction, thereby decreasing its activity. Taken together, our data indicate that loratadine regulates melanogenesis via Akt/MITF and PKC-ßII signaling, thereby leading to the inhibition of melanogenic proteins. The antimelanogenic effects of loratadine have potentially significant and useful roles in dermatologic practice, although further clinical studies will be required to test this.

Pancreatic Extraskeletal Osteosarcoma Metastasizing to the Scalp.

Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal soft-tissue neoplasm that accounts for approximately 1% of all soft-tissue sarcomas. Over 70% of these malignant tumor progress to local recurrence and metastasis. It commonly metastasizes to the lungs, lymph nodes, bone, and skin and has a poor survival outcome. Cutaneous metastasis is exceedingly rare and known to be a sign of widespread metastases. We present a 57-year-old woman who presented with a rapidly growing protuberant mass on the scalp that was finally diagnosed as metastatic ESOS from a primary pancreatic ESOS. To our knowledge, there has been no reported case of pancreatic ESOS metastasizing to the scalp.

Levator Aponeurosis and Muller Muscle Plication Reinforced With Levator Sheath Advancement for Blepharoptosis Correction.

The authors innovated the levator aponeurosis and Muller muscle plication reinforced with levator sheath advancement (AMPSA) for blepharoptosis correction. The orbital septum was opened 1 mm above its fusion with the levator aponeurosis. The preaponeurotic fat was retracted and the thickened part of the levator sheath was identified. Two plication sutures were made: medial suture at the medial border of the pupil and lateral between the lateral border of the pupil and the lateral limbus. A needle with 6-0 nylon thread first bit the tarsal plate approximately 1 mm below its upper border, then bit the levator aponeurosis and the Muller muscle together at 3 to 6 mm above the upper border of the tarsal plate. The needle bit 1 to 3 mm of the thickened part of the levator sheath and the suture was tied. A total of 116 eyes were operated on using levator aponeurosis and Muller muscle plication (AMP), and 79 eyes using AMPSA. The mean follow-up period was 11.4 months. In the AMP group, the postoperative marginal reflex distance-1 (MRD-1) (3.8 ±â€Š0.2 mm) was significantly greater than the preoperative MRD-1 (2.7 ±â€Š0.3 mm) (P < 0.001). In the AMPSA group, the postoperative MRD-1 (3.5 ±â€Š0.3 mm) was also significantly greater than the preoperative MRD-1 (1.7 ±â€Š0.4 mm) (P < 0.001). The improvement in MRD-1 was greater in the AMPSA group (1.7 ±â€Š0.4 mm) than in the AMP group (1.1 ±â€Š0.3 mm) (P < 0.001). The difference in the MRD-1 outcome between AMPSA and AMP (0.6 mm) was obtained by advancing the thickened part of the levator sheath. AMPSA may be an effective procedure for correcting blepharoptosis.

Osteogenesis of Adipose-Derived and Bone Marrow Stem Cells with Polycaprolactone/Tricalcium Phosphate and Three-Dimensional Printing Technology in a Dog Model of Maxillary Bone Defects.

Bone graft material should possess sufficient porosity and permeability to allow integration with native tissue and vascular invasion, and must satisfy oxygen and nutrient transport demands. In this study, we have examined the use of three-dimensional (3D)-printed polycaprolactone/tricalcium phosphate (PCL/TCP) composite material in bone grafting, to estimate the scope of its potential application in bone surgery. Adipose-derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) are known to enhance osteointegration. We hypothesized that a patient-specific 3D-printed solid scaffold could help preserve seeded ADSCs and BMSCs and enhance osteointegration. Diffuse osteogenic tissue formation was observed by micro-computed tomography with both stem cell types, and the ADSC group displayed similar osteogenesis compared to the BMSC group. In histological assessment, the scaffold pores showed abundant ossification in both groups. Reverse transcription polymerase chain reaction (RT-PCR) showed that the BMSC group had higher expression of genes associated with ossification, and this was confirmed by Western blot analysis. The ADSC- and BMSC-seeded 3D-printed PCL/TCP scaffolds displayed promising enhancement of osteogenesis in a dog model of maxillary bone defects.